The Transgenic Core provides state-of-the-art molecular tools to Project investigators. Centralizing these functions within a single Core derives substantial cost savings and ensures the proper and rigorous use of these approaches. First, numerous lines of transgenic and knockout mice, obtained from other laboratories, are required for the studies proposed in this PPG. The Core is responsible for breeding, genotyping, and maintaining the progeny for use by the individual Projects, as well as providing the appropriate control mice. Second, several new lines of transgenic and knockout mice, required for the PPG's Projects, will be made as part of this Core. Among these new lines are those that manipulate the expression of specific genes both temporally and spatially, in other words, inducible and cell-targeted mutations in brain. Our group has significant experience with these methods, which include the tetracycline gene regulation system and the Cre-loxP system. A major goal of the Core is to now adapt these methods to generate truly inducible, cell-targeted knockouts. Third, the Core provides Project investigators with herpes simplex virus vectors required for the research. In addition, the Core will work to improve the viral methodologies available, for example, using adeno-associated viral vectors, as well as viral vectors expressing Cre recombinase to induce a highly restricted gene knockout in the brain. Fourth, the PPG's Projects utilize DNA microarrays (both glass-based arrays and Affymetrix chips) to study differences in gene expression within particular brain regions of interest. The Core provides the arraying and data analysis for Project investigators. By centralizing this activity, we ensure a high quality of the array data and the ready ability to compare and contrast array findings among the various Projects. Indeed, the array data we've already accumulated have demonstrated common changes in gene expression in mice with mutations in the various proteins of interest to the five Projects.